Beta-oxidation is the metabolic process by which fatty acids, derived from fat by the actions of lipases, are converted to glucose via the formation of acetyl-CoA (Bebernitz and Schuster, Curr Pharm Des 8:1199-1227, 2002). A major source of Acetyl-CoA is fatty acid oxidation. Acetyl-CoA is a potent inhibitor of glucose oxidation via the activation of pyruvate dehydrogenase kinase (PDK), an inhibitor of the glycolytic enzyme pyruvate dehydrogenase complex (PDH-C). PDH is the rate limiting enzyme in the oxidation of glucose by converting pyruvate, derived from glucose in the glycolytic cycle, to Acety-CoA. A cardinal rule of energy metabolism is that glucose is the preferred fuel, the exception being the heart and brain that rely on FAO for 70% of their energy. When glucose becomes limited, such as in states of insulin resistance, the substrate for combustion is switched from glucose to fatty acids. This rule is known as the Randle Hypothesis (Diabetes Metab Rev 14:263-283, 1998). Importantly, according to the Randle hypothesis, inhibition of fatty acid metabolism (transport and/or oxidation) results in the stimulation of glucose oxidation and the inhibition of glucose production (gluconeogenesis). This is particularly important in the liver, the major site of gluconeogenesis.